Good Calories, Bad Calories

The new research would also mark the first time that HDL was measured in large populations, and this would further confuse the diet/heart-disease relationship. The hypothesis that HDL particles or the cholesterol in HDL protects against heart disease had first been proposed in 1951 by David Barr and Howard Eder of New York Hospital–Cornell Medical Center. It had been confirmed in a handful of small studies through the 1950s, and by Gofman in the last paper he published on lipoproteins and heart disease, as had the observation that when HDL was low triglycerides tended to be high, and vice versa, which suggested some underlying mechanism linking the two. Nonetheless, heart-disease researchers had paid little attention to HDL, as the NIH biostatistician Tavia Gordon later explained, because the idea of a “negative relation” between cholesterol and heart disease—high HDL cholesterol implies a low risk of heart disease—“simply ran against the grain.” “It was easy to believe that too much cholesterol in the blood could ‘overload’ the system and hence increase the risk of disease,” Gordon wrote, “but how could ‘too much’ of one part of the total cholesterol reduce the risk of disease? To admit that fact challenged the whole way of thinking about the problem.” Now HDL, too, would be measured in these populations.^*44

The results from the five studies were released in 1977 and divided into two publications, although Gordon had done the analyses for both. One reported on a comparison of nine hundred heart-disease cases with healthy controls from all five of the populations. The other addressed the prospective evidence from Framingham alone—measuring triglyceride, lipoprotein, and cholesterol levels in twenty-eight hundred subjects and then waiting four years to see how well these levels predicted the appearance of heart disease. The findings were consistent. Both analyses confirmed Gofman’s argument that total cholesterol said little about the risk of heart disease, and that the measurement of the triglycerides and cholesterol in the different lipoproteins was considerably more revealing. In men and women fifty and older, Gordon and his collaborators wrote in the Framingham paper, “total cholesterol per se is not a risk factor for coronary heart disease at all.” LDL cholesterol was a “marginal” risk factor, they reported. Triglycerides predicted heart disease in men and women in the analysis of cases from all five studies, but only in women in the Framingham analysis.

HDL was the “striking” revelation. Both analyses confirmed that the higher the HDL cholesterol the lower the triglycerides and the risk of heart disease. The inverse relationship between HDL and heart disease held true for every age group from forty-year-olds to octogenarians, in both men and women, and in every ethnic group from Framingham, Massachusetts, to Honolulu. “Of all the lipoproteins and lipids measured HDL had the largest impact on risk,” Gordon and his colleagues wrote. For those fifty and over, which is the age at which heart disease ceases to be a rare condition, HDL was the only reliable predictor of risk.

The finding that high HDL cholesterol was associated with a low risk of heart disease did not mean that raising HDL would lower risk, as Gordon and his colleagues noted, but it certainly suggested the possibility. Only a few studies had ever looked at the relationship of diet and lifestyle to HDL, and the results had suggested, not surprisingly, that anything that raised triglycerides would lower HDL, and vice versa. The “fragmentary information on what maneuvers will lead to an increase in HDL cholesterol levels,” Gordon and his collaborators wrote, “suggests that physical activity, weight loss and a low carbohydrate intake may be beneficial” (my italics).